Chronology-based architecture of descending circuits that underlie the development of locomotor repertoire after birth

Abstract

The emergence of new and increasingly sophisticated behaviors after birth is accompanied by dramatic increase of newly established synaptic connections in the nervous system. Little is known, however, of how nascent connections are organized to support such new behaviors alongside existing ones. To understand this, in the larval zebrafish we examined the development of spinal pathways from hindbrain V2a neurons and the role of these pathways in the development of locomotion. We found that new projections are continually layered laterally to existing neuropil, and give rise to distinct pathways that function in parallel to existing pathways. Across these chronologically layered pathways, the connectivity patterns and biophysical properties vary systematically to support a behavioral repertoire with a wide range of kinematics and dynamics. Such layering of new parallel circuits equipped with systematically changing properties may be central to the postnatal diversification and increasing sophistication of an animal’s behavioral repertoire.

eLife digest

Newborn babies have limited abilities. Indeed, most of our actions shortly after birth are the result of reflexes that serve our most basic need: to stay alive. As we get older, however, our behaviour gradually becomes more sophisticated. During this time, the billions of cells in our brain form new connections to build intricate ‘circuits’ of neurons that allow for more complicated thoughts and actions.

It is clear that the brain circuits that support new behaviours must develop in a way that does not interfere with the existing circuits that are vital for survival. However, the challenge has been to find a way to peer into a brain as it develops to see how these new circuits form.

In recent years, zebrafish have revolutionised research into neuronal circuits in animals. Developing over the course of a few days, these small transparent fish provide a window into the brain during the earliest stages of development. Indeed, the circuits of neurons that descend from the brain and connect to the spinal cord have already been mapped in these animals. Now, Pujala and Koyama have begun to follow the careful development of these ‘descending’ neurons, and relate it to the appearance of new behaviours in young zebrafish.

Time-lapse imaging with a fluorescent protein that is active only in specific descending neurons revealed that new circuits are laid down over existing ones, like the growth rings in a tree. Next, at different timepoints in zebrafish development, Pujala and Koyama traced these neurons backwards from the spine to the brain to identify which connections formed first. This showed that the spinal connections develop one after the other, in the same order that the neurons mature.

Next, Pujala and Koyama asked how the activity of neurons that mature early or late in development relates to specific behaviours in young zebrafish. Early-born circuits connect to neurons that produce powerful, reflex-driven, whole-body movements such as an escape response. The later circuits connect to different neurons through slower, less direct pathways; the late-born neurons also generate the refined movements that are acquired later in a zebrafish’s development and help the fish to explore its environment.

These findings show that descending circuits in zebrafish run parallel to each other, but with distinct connections and properties that allow them to control different kinds of movements. While this study was conducted using an animal model, a better understanding of how such circuits develop and the movements they control may one day aid the treatment of patients with neurodegenerative diseases or injuries where connections have been lost.